Brain Research Bulletin, Vol. 26, pp. 851-855. ® Pergamon Press plc, 1991. Printed in the U.S.A.
0361-9230/91 $3.00 + .00
Amniotic-Fluid Ingestion Enhances the Central
Analgesic Effect of Morphine
J. M. DI PIRRO, A. C. THOMPSON AND M. B. KRISTAL1
Department of Psychology, State University of New York at Buffalo, Buffalo, NY 14260
Received 26 November 1990
DI PIRRO, J. M., A. C. THOMPSON AND M. B. KRISTAL. Amniotic-fluid ingestion enhances the central analgesic effect of
morphine. BRAIN RES BULL 26(6) 851-855, 1991.—Amniotic fluid and placenta contain a substance (POEF) that when in-
gested enhances opioid-mediated analgesia produced by several agents (morphine injection, VaginalZcervical stimulation, late preg-
nancy, footshock), but not that produced by aspirin injection. The present series of experiments employed quaternary naltrexone,
an opioid antagonist that does not readily cross the blood-brain barrier, in conjunction with either peripheral or central administra-
tion of morphine, to determine whether amniotic-fluid ingestion (and therefore POEF ingestion) enhances opioid-mediated analge-
sia by affecting the central and/or peripheral actions of morphine. The results suggest that POEF affects only the central analgesic
effects of morphine.
POEF Analgesia Pain Rats Morphine Opioids Placenta Quaternary naltrexone
Amniotic fluid Placentophagia Naltrexone methobromide
INGESTION of a substance contained in amniotic fluid and pla-
centa, POEF (Placental Opioid-Enhancing Factor), enhances an-
algesia produced by late pregnancy, peripheral morphine injection,
footshock, and VaginaLZcervical stimulation in rats. However,
amniotic fluid ingestion, or placenta ingestion, not paired with
administration of an analgesic or an analgesia-producing proce-
dure, does not produce analgesia (3-8). Furthermore, this en-
hancement appears to be specific to opioid-mediated analgesia:
treatment with opioid antagonists such as naltrexone and nalox-
one blocks the enhancement (6,7), and POEF ingestion does not
enhance nonopioid-mediated analgesia produced by aspirin injec-
tion in naltrexone-treated rats (5).
The present studies represent a step toward elucidating the
mechanism by which POEF enhances opioid-mediated analgesia
by investigating whether POEF enhances the central or periph-
eral action of opioids. In order to localize the action of POEF,
we used a quaternary derivative of the opiate antagonist naltrex-
one, naltrexone methobromide (QN). QN penetrates the blood-
brain barrier less readily than its tertiary counterpart and can thus
be used to discriminate peripheral from central opioid action
(2,12). Morphine has both peripheral and central actions, al-
though the more important locus, for analgesia, is central (9,13).
Our attempt to determine whether POEF acts centrally, periph-
erally, or both centrally and peripherally, on morphine-mediated
analgesia rested on three premises, (a) Enhancement of system-
ic-morphine-mediated analgesia by ingested POEF during a block-
ade of peripheral opiate receptors (by peripheral administration
of QN), would indicate a central opioid mechanism. Similarly,
(b) enhancement by ingested POEF of analgesia produced by
centrally administered morphine during a blockade of peripheral
opiate receptors (by peripheral administration of QN), would
also support the contention of at least a central action for POEF.
Finally, (c) failure of ingested POEF to enhance systemic-mor-
phine-mediated analgesia during a blockade of central opiate re-
ceptor sites (by central administration of QN) would provide
strong evidence for only a central action of POEF.
EXPERIMENT 1
The first experiment was designed to examine whether re-
stricting morphine to its central action still permitted analgesia
enhancement by ingestion of POEF in amniotic fluid. Enhance-
ment of systemically administered morphine was assessed while
peripheral opioid receptors were blocked by systemically admin-
istered QN.
METHOD
Subjects
The subjects were 32 nulliparous, female, Long-Evans (hood-
ed) rats, 75-105 days of age, weighing 256±3.6 g. The rats
were housed individually in 24.5 × 18 × 18-cm suspended wire-
mesh cages in a colony maintained on a 14-h on∕10-h off light-
dark cycle (lights on at 0500 h, EST). All subjects had unlimited
access to food (Agway Prolab Rat/Mouse/Hamster Formula 3000)
and water, except for a three-hour period prior to, and during,
testing.
Apparatus
Analgesia (increase in pain threshold) was measured using a
radiant-heat tail-flick algesiometer described previously (4,8).
Pain threshold was represented as the mean of the last 3 of 4
tail-flick latency (TFL) trials, recorded at 30-s intervals. Trials
‘Requests for reprints should be addressed to Dr. Mark B. Kristal, Department of Psychology, SUNY at Buffalo, Buffalo, NY 14260.
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